Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 79
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Biomed Pharmacother ; 127: 110098, 2020 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-32299028

RESUMO

N6-methyladenosine (m6A) is the most abundant RNA modification; m6A modifications are installed by methyltransferases, removed by demethylases and recognized by reader proteins. M6A plays crucial roles in a variety of biological processes by regulating target RNA translation, splicing, nuclear export, and decay. Since the establishment of methylated RNA immunoprecipitation-sequencing methodology, over three hundred articles about m6A modulators, including "writers", "erasers" and "readers", have been reported in the last four years. In addition, an increasing number of molecular mechanisms underlying m6A RNA methylation in human cancers have been comprehensively clarified. The recently emerged molecular mechanisms of m6A modulators in cancer cell proliferation, cell cycle progression, migration and invasion, apoptosis, and autophagy remain to be summarized. Hence, this review specifically summarizes these recent advances in the understanding of m6A molecular mechanisms in tumorigenesis and cancer progression. In addition, we discuss the prospect of using an m6A methylation modulator as a new diagnostic biomarker and therapeutic target for human cancers.

2.
Genome Biol ; 21(1): 99, 2020 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-32345342

RESUMO

BACKGROUND: Influenza is a severe respiratory illness that continually threatens global health. It has been widely known that gut microbiota modulates the host response to protect against influenza infection, but mechanistic details remain largely unknown. Here, we took advantage of the phenomenon of lethal dose 50 (LD50) and metagenomic sequencing analysis to identify specific anti-influenza gut microbes and analyze the underlying mechanism. RESULTS: Transferring fecal microbes from mice that survive virulent influenza H7N9 infection into antibiotic-treated mice confers resistance to infection. Some gut microbes exhibit differential features to lethal influenza infection depending on the infection outcome. Bifidobacterium pseudolongum and Bifidobacterium animalis levels are significantly elevated in surviving mice when compared to dead or mock-infected mice. Oral administration of B. animalis alone or the combination of both significantly reduces the severity of H7N9 infection in both antibiotic-treated and germ-free mice. Functional metagenomic analysis suggests that B. animalis mediates the anti-influenza effect via several specific metabolic molecules. In vivo tests confirm valine and coenzyme A produce an anti-influenza effect. CONCLUSIONS: These findings show that the severity of influenza infection is closely related to the heterogeneous responses of the gut microbiota. We demonstrate the anti-influenza effect of B. animalis, and also find that the gut population of endogenous B. animalis can expand to enhance host influenza resistance when lethal influenza infection occurs, representing a novel interaction between host and gut microbiota. Further, our data suggest the potential utility of Bifidobacterium in the prevention and as a prognostic predictor of influenza.

3.
Int Immunopharmacol ; 78: 106066, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31835087

RESUMO

Intestinal barrier dysfunction is a trigger for sepsis progression. NLRP3 inflammasome and RhoA contribute to sepsis and intestinal inflammation. The current study aimed to explore the effects of Astragaloside IV (AS-IV), a bioactive compound from Astragalus membranaceus, on sepsis-caused intestinal barrier dysfunction and whether NLRP3 inflammasome and RhoA are involved. Septic mice modeled by cecal ligation and puncture (CLP) operation were administered with 3 mg/kg AS-IV intravenously. AS-IV decreased mortality, cytokines release, I-FABP secretion, intestinal histological score and barrier permeability, and increased tight junction (TJ) expression in intestine in CLP model. Also, in Caco-2 cells subjected to lipopolysaccharide (LPS), 200 µg/mL AS-IV co-incubation reduced cytokines levels and enhanced in vitro gut barrier function without cytotoxicity. Subsequently, NLRP3 inflammasome and RhoA were highly activated both in intestinal tissue in vivo and in Caco-2 cells in vitro, both of which were significantly suppressed by AS-IV treatment. In addition, the benefits of AS-IV on Caco-2 monolayer barrier were largely counteracted by RhoA agonist CN03 and NLRP3 gene overexpression, respectively. Furthermore, LPS-induced NLRP3 inflammasome activation was abrogated by RhoA inhibitor C3 exoenzyme. However, NLRP3 knockdown by siRNA hardly affected RhoA activation in Caco-2 cells. These data suggest that AS-IV protects intestinal epithelium from sepsis-induced barrier dysfunction via inhibiting RhoA/NLRP3 inflammasome signal pathway.

4.
Gastric Cancer ; 23(3): 483-496, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31853750

RESUMO

BACKGROUND: Epigenetic aberrations of tumor suppressor genes (TSGs), particularly DNA methylation, are frequently involved in the pathogenesis of gastric cancer (GC). Through a methylome study, we identified eIF4EBP3 as a methylated gene in GC. However, the role of eIF4EBP3 in GC progression has not been explored. METHODS: The expression and promoter region methylation of eIF4EBP3 in GC and healthy tissues were analyzed in public datasets. eIF4EBP3 expression in GC was detected by semi-quantitative RT-PCR, western blot and immunohistochemistry. We also studied epigenetic alterations and functions in GC. The effects of eIF4EBP3 on cell proliferation, migration and invasion were conducted by functional experiments in vitro and in vivo. Label-free proteomic analysis was applied to identify targets of eIF4EBP3. RESULTS: The expression level of eIF4EBP3 was downregulated in gastric cancer due to promoter region methylation, and was associated with poor survival and tumor progression. Ectopic expression of eIF4EBP3 significantly inhibited tumor cell growth, migration and invasion both in vitro and in vivo. Label-free proteomic analysis indicated eIF4EBP3 downregulated the protein level of ß-catenin, which was confirmed by western blot. Overexpression of ß-catenin reversed the inhibitory effects of eIF4EBP3 on cell growth and migration, indicating that eIF4EBP3 acts on GC cells by targeting the eIF4E/ß-catenin axis. CONCLUSION: These results suggest that eIF4EBP3 is a novel TSG methylated in gastric cancer that may play important roles in GC development and liver metastasis and indicate eIF4EBP3 as a potential metastasis and survival biomarker for GC.

5.
Carcinogenesis ; 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31784734

RESUMO

Forkhead box D3 (FOXD3), an important member of the forkhead box transcription factor family, has many biological functions. However, the role and signaling pathways of FOXD3 in colorectal cancer (CRC) are still unclear. We examined FOXD3 expression and methylation in normal colon mucosa, CRC cell lines, and primary tumors by RT-PCR, methylation-specific PCR, and bisulfite genomic sequencing. We also evaluated its tumor-suppressive function by examining its modulation of apoptosis under endoplasmic reticulum (ER) stress in CRC cells. The FOXD3 target signal pathway was identified by western blotting, immunofluorescence, and chromatin immunoprecipitation. We found that FOXD3 was frequently methylated and silenced in CRC cell lines and was downregulated in CRC tissues compared with paired adjacent non-tumor tissues. Meanwhile, low FOXD3 protein expression was significantly correlated with poor histopathological grading, lymph node metastasis, and poor prognosis of patients, indicating its potential as a tumor marker that may be of potential value as a therapeutic target for CRC. Moreover, restoration of FOXD3 expression inhibited the proliferation and migration of tumor cells. FOXD3 also increased mitochondrial apoptosis through the unfolded protein response under ER stress. Furthermore, we found that FOXD3 could bind directly to the promoter of p53 and enhance its expression. Knockdown of p53 impaired the effect of apoptosis induced by FOXD3. In conclusion, we showed for the first time that FOXD3, which is frequently methylated in CRC, acted as a tumor suppressor inducing tumor cell apoptosis under ER stress via p53.

6.
Foodborne Pathog Dis ; 2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31829731

RESUMO

The incidence of hepatitis A virus (HAV) infection has been low in developed countries for decades; however, many adults in these countries are susceptible to HAV infection. In recent years, the global trade of food products originating from HAV-endemic countries resulted in HAV outbreaks associated with imported foods in developed countries. This article aims to review the characteristics of selected HAV outbreaks associated with imported food in developed countries during 2012-2018, and discusses improvements in global public health capabilities and new tools for effective detection, control, and prevention of HAV outbreaks.

7.
Int J Med Sci ; 16(8): 1149-1156, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31523178

RESUMO

Background Sepsis, a leading cause of death in intensive care units, is generally associated with vascular dysfunction. However, its pathophysiological process has not been fully clarified, lacking in-depth knowledge of its pathophysiological process may hinder the improvement of diagnosis and therapy for sepsis. Hence, as the key parts of the vascular wall, the interaction between endothelial cells (ECs) and smooth muscle cells (SMCs) under septic situation need to be further studied. Methods ECs and SMCs were co-cultured using Transwell plates. Lipopolysaccharide (LPS) was used to induce sepsis. A scratch-wound assay was used to assess cell migration, and western blotting was used to assess the level of redifferentiation of SMCs as well as the expression of PDGFR-ß and IQGAP1. Results Co-culture with ECs reduced the redifferentiation of SMCs induced by LPS (10 µg/ml), which was characterized by increased migration ability and decreased expression of contractile proteins (e.g., SM22 and α-SMA). The production of TNF-α could decrease the level of PDGFR-ß in SMCs. Treatment of SMCs with the PDGFR-ß inhibitor imatinib (5 µM) was able to counteract LPS-induced SMC redifferentiation and reduce IQGAP1 protein expression, especially when SMCs were co-cultured with ECs. Conclusion The phenotype of vascular SMCs co-cultured with ECs was modulated by IQGAP1 through the PDGFR-ß pathway, which may lead to vascular remodeling and homeostasis in LPS-induced intravascular injury. This pathway could be a novel target for the treatment of vascular damage.


Assuntos
Músculo Liso Vascular/citologia , Receptor beta de Fator de Crescimento Derivado de Plaquetas/metabolismo , Proteínas Ativadoras de ras GTPase/metabolismo , Técnicas de Cocultura , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Endotélio Vascular/citologia , Humanos , Lipopolissacarídeos/toxicidade , Músculo Liso Vascular/efeitos dos fármacos , Fenótipo , Sepse/metabolismo , Sepse/patologia , Transdução de Sinais , Fator de Necrose Tumoral alfa/metabolismo
8.
Int J Infect Dis ; 87: 8-12, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31357055

RESUMO

Tenofovir disoproxil fumarate (TDF) is a prodrug of tenofovir, and after being administered orally, it converts to tenofovir in the blood. With the increasing use of TDF in women for treatment and prevention of mother-to-child transmission (MTCT) of both human immunodeficiency virus (HIV) and hepatitis B virus (HBV), or the pre-exposure prophylaxis (PrEP) for HIV, many nursing mothers have to understand the risk of exposure to tenofovir via breastmilk and make the decision about breastfeeding while on TDF treatment. Despite the safety record of TDF in pregnancy, some guidelines recommend against its use during breastfeeding. In this paper, we compared the dosage levels of tenofovir exposure in fetuses, breastfed infants, and children receiving tenofovir treatment. We found that breastfed infants were exposed to only 0.5%-16% of the tenofovir dosage that fetuses experienced via placental transfer, and 0.01-0.04% of the recommended weight-adjusted therapeutic dose. The assessment of toxicity risk from the dose perspective is an important and natural way of addressing safety concerns about exposure to tenofovir via breastfeeding. Based on the safety data from fetuses and children with tenofovir exposure, and the comparatively negligible exposure dosage from breastfeeding, our study supports mothers on TDF treatment should be encouraged to breastfeed.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/prevenção & controle , Transmissão Vertical de Doença Infecciosa/prevenção & controle , Complicações Infecciosas na Gravidez/prevenção & controle , Tenofovir/uso terapêutico , Animais , Fármacos Anti-HIV/análise , Antivirais/análise , Antivirais/uso terapêutico , Feminino , Infecções por HIV/tratamento farmacológico , Hepatite B/prevenção & controle , Hepatite B/virologia , Humanos , Masculino , Leite Humano/química , Gravidez , Complicações Infecciosas na Gravidez/virologia , Tenofovir/análise
9.
Cell Death Dis ; 10(6): 444, 2019 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-31168049

RESUMO

Hepatocellular carcinoma (HCC) is a highly heterogeneous, multigene-driven malignant tumor. ZNF384 is an overexpressed gene with a high frequency of alteration in HCC, but research on the function of ZNF384 in HCC is lacking. In this study, the expression level of ZNF384 in HCC was analyzed through immunohistochemical (IHC) staining, Western blot analysis and qRT-PCR. We also generated ZNF384 knockdown and knockout HCC cell lines using short hairpin RNA (shRNA) and CRISPR/Cas9 systems. MTS, colony formation, and 5-ethynyl-20-deoxyuridine (EdU) assays; flow cytometry; and a xenograft mouse model were used to evaluate the effects of ZNF384 on cell proliferation. Western blot analysis, a dual luciferase reporter assay and a ChIP assay were performed to explore the potential mechanism. We found that overexpression of ZNF384 in HCC and elevated expression of ZNF384 in HCC tissues was significantly correlated with tumor recurrence (P = 0.0097). Kaplan-Meier survival analysis revealed that high expression levels of ZNF384 were correlated with poor overall survival (P = 0.0386). Downregulation of ZNF384 expression suppressed HCC cell proliferation by inhibiting the expression of Cyclin D1. These findings suggest that ZNF384 tends to act as an oncogene in the development of HCC. ZNF384 promotes the proliferation of HCC cells by directly upregulating the expression of Cyclin D1 and might serve as a prognostic predictive factor for HCC patients.

10.
BMC Cancer ; 19(1): 629, 2019 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-31238895

RESUMO

BACKGROUND: This study aimed to evaluate the value of chitinase activity in prognosticating the occurrence of metastasis in and prognosis of patients with colorectal cancer (CRC). METHODS: The chitinase activity in four different groups, namely 335 CRC patients without distant metastasis at their first visit (Group 1), 51 patients with CRC having synchronous liver metastasis (Group 2), 100 healthy age-matched controls (Group 3) and 40 patients with liver cancer (Group 4), were assayed using an enzyme-linked immunosorbent assay. The Cox proportional hazards ratio model and Kaplan-Meier curve were used to identify the association between chitinase activity and the clinical outcome of CRC patients without metastasis in the training set and testing set at their first visit. An in vitro Transwell experiment was performed to evaluate the migration of colon cancer cells. RESULTS: Patients with high chitinase activity had a significantly higher metastasis risk than those with low chitinase activity in the training and testing sets during follow-up, both at stage I/II and stage III. Further, multivariate analysis revealed that chitinase activity was an independent risk factor prognosticating liver metastases (P = 0.001). The combination of chitinase activity and lymph node metastasis status increased the accuracy of the prognosis of liver metastases after radical resection (P = 0.454E-011). In addition, chitinase promoted CRC cell migration in vitro. CONCLUSIONS: Chitinase activity can prognosticate the occurrence of metastasis in patients with CRC. Moreover, the combination of chitinase activity and N stage increased the power of prognosticating the occurrence of metastasis. Inhibiting chitinase activity may serve as a new strategy to treat metastases of CRC.


Assuntos
Quitinases/sangue , Neoplasias do Colo/enzimologia , Neoplasias do Colo/patologia , Neoplasias Hepáticas/secundário , Neoplasias Retais/enzimologia , Neoplasias Retais/patologia , Biomarcadores Tumorais/sangue , Estudos de Casos e Controles , Linhagem Celular Tumoral , Movimento Celular , Neoplasias do Colo/mortalidade , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/enzimologia , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Neoplasias Retais/mortalidade , Estudos Retrospectivos
11.
Am J Cancer Res ; 9(4): 752-764, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31106001

RESUMO

The reversible N6-methyl-adenosine (m6A) modification of messenger RNAs (mRNAs) has generated much interest in the field of stem cell modulation in recent years. Meanwhile, mounting evidence has shown that many physiopathological processes concerning cell death and survival harbor this chemical mark. Our review provides an overview of the m6A epitranscriptomic field and the updated mechanisms of m6A decoration in stem cell regulation. Furthermore, we focus on the role of m6A in DNA damage and the immune response, cell apoptosis, autophagy, and senescence, followed by recent advancements in m6A-induced viral replication. The function of abundant RNA-binding proteins (RBPs) identified in m6A regulatory systems will also be discussed in this review, highlighting their far-reaching implications in cellular m6A machinery and disease treatment.

12.
RNA Biol ; 16(8): 991-1000, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31107151

RESUMO

RNA epigenetics has received a great deal of attention in recent years, and the reversible N6-methyladenosine (m6A) modification on messenger RNAs (mRNAs) has emerged as a widespread phenomenon. The vital roles of m6A in diverse biological processes are dependent on many RNA-binding proteins (RBPs) with 'reader' or 'nonreader' functions. Moreover, m6A effector proteins affect cellular processes, such as stem cell differentiation, tumor development and the immune response by controlling signal transduction. This review provides an overview of the interactions of m6A with various RBPs, including the 'reader' proteins (excluding the YT521-B homology (YTH) domain proteins and the heterogeneous nuclear ribonucleoproteins (hnRNPs)), and the functional 'nonreader' proteins, and this review focuses on their specific RNA-binding domains and their associations with other m6A effectors. Furthermore, we summarize key m6A-marked targets in distinct signaling pathways, leading to a better understanding of the cellular m6A machinery.

13.
Anal Chim Acta ; 1071: 1-7, 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31128750

RESUMO

Quantitatively paper-based senor is performed with simple distance-readout on mixed cellulose ester (MCE) filter paper based on acetylcholinesterase (AChE)-mediated alginate hydrogel. The method is accomplished with the aid of the inhibition effect of target samples on the AChE enzyme-catalyzed hydrolysis of acetylcholine, which changes the pH value of the solution to release Ca2+ and trigger alginate hydrogelation. The viscosity of the solution is thus regulated with the presence of target samples in the reaction mixture, leading to a significant change in the diffusion diameter of the solution spotted on the filter paper. The concentration in the sample is quantitatively determined by ruler-measureable diffusion diameter of the spot on the paper. With successfully application for quantitatively sensing of organophosphorus pesticides (OPs), we show that the method exhibits excellent reproducibility with RSD (n = 5) as low as 0.09% and good selectivity for detection of OPs. The dynamic range of the method is up to 66.7 ng/mL with the limit-of-detection (LOD) of 3.3 ng/mL. The present study provides a new approach for developing paper-based sensors with quantitative distance-readout, by utilizing enzymatic inhibition to modulate liquid viscosity, which would be of value for target detection in complex samples.


Assuntos
Acetilcolinesterase/química , Alginatos/química , Hidrogéis/química , Compostos Organofosforados/análise , Papel , Praguicidas/análise , Acetilcolina/química , Técnicas Biossensoriais/instrumentação , Técnicas Biossensoriais/métodos , Difusão , Contaminação de Alimentos/análise , Limite de Detecção , Malus/química , Reprodutibilidade dos Testes , Viscosidade
14.
Aging Cell ; 18(4): e12961, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31012223

RESUMO

Cav1.2 is the pore-forming subunit of L-type voltage-gated calcium channel (LTCC) that plays an important role in calcium overload and cell death in Alzheimer's disease. LTCC activity can be regulated by estrogen, a sex steroid hormone that is neuroprotective. Here, we investigated the potential mechanisms in estrogen-mediated regulation of Cav1.2 protein. We found that in cultured primary neurons, 17ß-estradiol (E2) reduced Cav1.2 protein through estrogen receptor α (ERα). This effect was offset by a proteasomal inhibitor MG132, indicating that ubiquitin-proteasome system was involved. Consistently, the ubiquitin (UB) mutant at lysine 29 (K29R) or the K29-deubiquitinating enzyme TRAF-binding protein domain (TRABID) attenuated the effect of ERα on Cav1.2. We further identified that the E3 ligase Mdm2 (double minute 2 protein) and the PEST sequence in Cav1.2 protein played a role, as Mdm2 overexpression and the membrane-permeable PEST peptides prevented ERα-mediated Cav1.2 reduction, and Mdm2 overexpression led to the reduced Cav1.2 protein and the increased colocalization of Cav1.2 with ubiquitin in cortical neurons in vivo. In ovariectomized (OVX) APP/PS1 mice, administration of ERα agonist PPT reduced cerebral Cav1.2 protein, increased Cav1.2 ubiquitination, and improved cognitive performances. Taken together, ERα-induced Cav1.2 degradation involved K29-linked UB chains and the E3 ligase Mdm2, which might play a role in cognitive improvement in OVX APP/PS1 mice.

15.
Sensors (Basel) ; 19(5)2019 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-30871069

RESUMO

Wearable electronic sensing devices are deemed to be a crucial technology of smart personal electronics. Strain and pressure sensors, one of the most popular research directions in recent years, are the key components of smart and flexible electronics. Graphene, as an advanced nanomaterial, exerts pre-eminent characteristics including high electrical conductivity, excellent mechanical properties, and flexibility. The above advantages of graphene provide great potential for applications in mechatronics, robotics, automation, human-machine interaction, etc.: graphene with diverse structures and leverages, strain and pressure sensors with new functionalities. Herein, the recent progress in graphene-based strain and pressure sensors is presented. The sensing materials are classified into four structures including 0D fullerene, 1D fiber, 2D film, and 3D porous structures. Different structures of graphene-based strain and pressure sensors provide various properties and multifunctions in crucial parameters such as sensitivity, linearity, and hysteresis. The recent and potential applications for graphene-based sensors are also discussed, especially in the field of human motion detection. Finally, the perspectives of graphene-based strain and pressure sensors used in human motion detection combined with artificial intelligence are surveyed. Challenges such as the biocompatibility, integration, and additivity of the sensors are discussed as well.


Assuntos
Inteligência Artificial , Grafite/química , Nanoestruturas/química
16.
Talanta ; 194: 925-929, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30609626

RESUMO

To develop a strategy for visualizing palladium species in the biological system, several turn-on bioluminescent probes were designed and synthesized by using a Pd-induced reductive reaction herein. Such probes exhibited high sensitivity (detection limit: 0.5 µM) and excellent selectivity toward Pd2+in vitro. In particular, probe 2 was identified as a viable molecule with the capability of visualizing the fluctuations of level and distribution of Pd2+ in living cells and animals, which provides a valuable tool for tracing Pd2+ in biological system.


Assuntos
Luciferases/metabolismo , Substâncias Luminescentes/química , Imagem Óptica/métodos , Paládio/análise , Animais , Linhagem Celular , Sobrevivência Celular , Limite de Detecção , Medições Luminescentes , Camundongos , Paládio/química
17.
J Cell Physiol ; 234(6): 8233-8240, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30370545

RESUMO

Metastatic dissemination represents the final stage of tumor progression as well as the principal cause of cancer-associated deaths. Calpains are a conserved family of calcium-dependent cysteine proteinases with ubiquitous or tissue-specific expression. Accumulating evidence indicates a central role for calpains in tumor migration and invasion via participating in several key processes, including focal adhesion dynamics, cytoskeletal remodeling, epithelial-to-mesenchymal transition, and apoptosis. Activated after the increased intracellular calcium concentration ( [ Ca 2 + ] i ) induced by membrane channels and extracellular or intracellular stimuli, calpains induce the limited cleavage or functional modulation of various substrates that serve as metastatic mediators. This review covers established literature to summarize the mechanisms and underlying signaling pathways of calpains in cancer metastasis, making calpains attractive targets for aggressive tumor therapies.

18.
J Cell Physiol ; 234(5): 5564-5577, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30317588

RESUMO

DIRAS family is a group of GTPases belonging to the RAS superfamily and shares homology with the pro-oncogenic Ras GTPases. Currently, accumulating evidence show that DIRAS family members could be identified as putative tumor suppressors in various cancers. The either lost or reduced expression of DIRAS proteins play an important role in cancer development, including cell growth, migration, apoptosis, autophagic cell death, and tumor dormancy. This review focuses on the latest research regarding the roles and mechanisms of the DIRAS family members in regulating Ras function, cancer development, assessing potential challenges, and providing insights into the possibility of targeting them for therapeutic use.

19.
Talanta ; 189: 377-382, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30086934

RESUMO

Rapid, low-cost and efficient assays for penicillinase activity and inhibition are of vital importance for therapeutics and diagnostics of bacterial resistance to antibiotics. Herein we report a novel approach for on-line enzyme assays for penicillinase utilizing capillary electrophoresis-integrated immobilized enzyme reactors (CE-IMERs). The CE-IMERs are fabricated based on penicillinase-mediated alginate hydrogelation, allowing single-step in-situ encapsulation of enzymes without any additional manipulation process. We show that the fabricated CE-IMERs have high enzyme loading capacity with approximately 61.8% of the original penicillinase in the sol mixture being encapsulated in the "egg-box" hydrogel matrix. Excellent intraday and interday stability and batch-to-batch reproducibility are proved, indicating the reliability of our method for accurate on-line enzyme assays for penicillinase. Enzymatic activities and inhibition of immobilized penicillinase are analyzed, the results of which are in good agreement with those using free enzymes. The proposed method is successfully used for determination of penicillin in pork samples, indicating the potential applications for analysis of complicated real samples.


Assuntos
Alginatos/química , Eletroforese Capilar/métodos , Ensaios Enzimáticos/métodos , Enzimas Imobilizadas/metabolismo , Hidrogéis/química , Microtecnologia/instrumentação , Penicilinase/metabolismo , Enzimas Imobilizadas/química , Ácido Glucurônico/química , Ácidos Hexurônicos/química , Penicilinase/química , Penicilinas/análise , Carne Vermelha/análise
20.
Sci Rep ; 8(1): 9963, 2018 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-29967433

RESUMO

Lipopolysaccharide (LPS) can lead to vascular endothelial barrier dysfunction, which often results in acute lung injury and acute respiratory distress syndrome. However, the effects of different concentrations of LPS on human pulmonary microvascular endothelial barrier function and the involvement of the phosphatidylinositol-3-kinase-serine/threonine kinase (PI3K/Akt) pathway in this process remain unclear. Human pulmonary microvascular endothelial cells (HPMECs) were stimulated with different doses of LPS, and barrier function was examined by determining cell monolayer permeability, cell migration, and the expression of intercellular junction proteins (VE-Cadherin, Claudin-5, and Connexin-43). LY294002 was used to inhibit PI3K to verify the role of the PI3K/Akt pathway in the regulation of barrier function in HPMECs stimulated by LPS. Low doses of LPS increased HPMEC migration, up-regulated VE-Cadherin and Claudin-5 expression, down-regulated Connexin-43 expression, and promoted Akt phosphorylation, which could collectively decrease monolayer permeability. In contrast, high doses of LPS suppressed HPMEC migration, down-regulated the expression of VE-Cadherin and Claudin-5, up-regulated Connexin-43 expression, and reduced Akt phosphorylation, which could collectively increase monolayer permeability. LPS has a biphasic effect on HPMEC barrier function through the PI3K/Akt pathway, and this effect is concentration-dependent.


Assuntos
Células Endoteliais/efeitos dos fármacos , Lipopolissacarídeos/administração & dosagem , Pulmão/citologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Permeabilidade Capilar/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Células Cultivadas , Cromonas/farmacologia , Claudina-5/metabolismo , Conexina 43/metabolismo , Relação Dose-Resposta a Droga , Células Endoteliais/metabolismo , Endotélio Vascular/citologia , Humanos , Junções Intercelulares/efeitos dos fármacos , Junções Intercelulares/metabolismo , Morfolinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA